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Synthesis, X-ray, Hirshfeld surface analysis, exploration of DNA binding, urease enzyme inhibition and anticancer activities of novel adamantane-naphthyl thiourea conjugate.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2021 Apr; Vol. 109, pp. 104707. Date of Electronic Publication: 2021 Feb 09. - Publication Year :
- 2021
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Abstract
- 1-(adamantane-1-carbonyl-3-(1-naphthyl)) thiourea (C <subscript>22</subscript> H <subscript>24</subscript> N <subscript>2</subscript> OS (4), was synthesized by the reaction of freshly prepared adamantane-1-carbonyl chloride from corresponding acid (3) with ammonium thiocyanate in 1:1 M ratio in dry acetone to afford the adamantane-1-carbonyl isothiocyanate (2) in situ followed by treatment with 1-naphthyl amine (3). The structure was established by elemental analyses, FTIR, <superscript>1</superscript> H, <superscript>13</superscript> C NMR and mass spectroscopy. The molecular and crystal structure were determined by single crystal X-ray analysis. It belongs to triclinic system P - 1 space group with a = 6.7832(5) Å, b = 11.1810(8) Å, c = 13.6660(10) Å, α = 105.941(6)°, β = 103.730(6)°, γ = 104.562(6)°, Z = 2, V = 910.82(11) Å <superscript>3</superscript> . The naphthyl group is almost planar. In the crystal structure, intermolecular CH···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R <subscript>2</subscript> <superscript>2</superscript> (14) ring motifs, while the intramolecular NH···O hydrogen bonds enclose S(6) ring motifs, in which they may be effective in the stabilization of the structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H … H (59.3%), H … C/C … H (19.8%) and H … S/S … H (10.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. DFT, molecular docking and urease inhibition studies revealed stability and electron withdrawing nature of 4 as compared to DNA base pairs and residues of urease. The DNA binding results from docking, UV- visible spectroscopy, and viscosity studies indicated significant binding of 4 with the DNA via intercalation and groove binding. Further investigation of the compound was done on hepatocellular carcinoma; Huh-7 cell line as well as normal human embryonic kidney; Hek-293 cell line. The compound showed significant cytotoxic activity against Huh-7 cells in comparison to normal Hek-293 cells indicating selective cytotoxicity towards cancer cells.<br /> (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Subjects :
- Adamantane chemical synthesis
Adamantane pharmacology
Antineoplastic Agents chemical synthesis
Cell Line, Tumor
Cell Survival
Crystallography, X-Ray
DNA chemistry
Gene Expression Regulation, Enzymologic drug effects
Humans
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Thiourea chemical synthesis
Thiourea chemistry
Thiourea pharmacology
Urease genetics
Adamantane chemistry
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Thiourea analogs & derivatives
Urease metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 109
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33639362
- Full Text :
- https://doi.org/10.1016/j.bioorg.2021.104707